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Institute for Cardiovascular Disease Research

Project 4: Heart and Stress

Stress is a contributing factor to high blood pressure, which can eventually cause heart failure. Heart failure is a leading cause of illness, death and escalating health care costs across the nation and in the institute's home state of South Carolina.

Connections Between Chronic Stress and Heart Failure

One type of heart failure that is increasing disproportionately is heart failure where the heart pumps normally but is too stiff to fill properly, called heart failure with preserved ejection fraction. 

This project seeks to provide insight into pathways that contribute to this common form of heart failure, the onset of which we believe to be exacerbated and accelerated by stress, and provide the research foundation for a new way of treating and preventing heart failure with preserved ejection fraction.

Project Significance

  • This research will uncover new understandings of how this particular form of heart failure is affected by stress.

  • Through our interdisciplinary approach combining academic research with the ways it can apply in a clinical setting, we seek to find new treatments for this form of heart failure to reduce its mortality and morbidity rates. 

Research Innovation 

This study will be the first to strategically target how heart failure with preserved ejection fracture starts on the molecular level. The interdisciplinary nature of this project allows the work to then go beyond where many purely academic research undertakings stop, by extending findings to real-world clinical applications to identify possible treatments and medication for this form of heart failure.


Research Aims

  1. We aim to establish that the inflection point from LVPO (left ventricular pressure overload) to HFpEF (heart failure with preserved ejection fraction) is NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3) inflammasone induction which can be controlled by transgenic conditional constructs.

  2. We aim to determine that superimposing CUS (chronic unpredictable stress) with LVPO will accelerate the progression to HFpEF and interruption of NLRP3 will prevent this coactivation. process. Translational relevance will be established by utilizing an NLRP3 inhibitor with LVPO and CUS.

Hypothesis: The fundamental molecular switch in LVPO is NLRP3 induction causing a cascade of profibrotic events leading to HFpEF progression whereby chronic, unpredictable stress will cause a feedforward synergistic acceleration of this process.

Goal: To move the field forward by establishing that while systemic inflammation may not be an operative pathway for HFpEF, localized metabolic stress and NLRP3 induction is a key molecular event in the development and progression of this heart failure process

Vision: We will be the first to develop tissue/cell specific silencing of NLRP3 and identify that NLRP3 is essential for the development of HFpEF, and then pivot the small molecule NLRP3 inhibitor (OLT1171) for use in HFpEF.


SC Impact

While this research improves the lives of anyone who has cardiovascular disease or knows someone with cardiovascular disease in South Carolina—a high percentage of the population—certain groups will benefit greatly from this focus area and the institute's work at large.

Women and the Female Population

This research will improve the lives of anyone who has cardiovascular disease or knows someone with cardiovascular disease in South Carolina. However, certain groups will greatly benefit from our focus area and the institute's work at large.

Black and African American Communities

High blood pressure disproportionately affects African American communities. This community experiences high heart failure rates despite health providers meeting standard of care guidelines. The institute will shed light on how body responses to everyday situations increase the likelihood of cardiovascular disease in these populations.

Veterans and Those Suffering from PTSD or Trauma

Exposure to trauma affects the body in significant ways, especially the heart and vascular system. Veterans are at higher risk of having a new onset of heart disease compared with non-veterans. This research contributes directly to improving the lives of veterans and those with trauma or PTSD, while adding to the overall knowledge base of care for veterans.


Notable Awards, Outcomes and Practical Uses for this Research 

  • 8 patents and several million dollars generated in collaborative industry-NIH ventures
  • Funded by the National Institutes of Health and the U.S. Veterans Health Administration continually for more than 2 decades
  • Dr. Spinale helped to spearhead the new generation of heart failure medications: early translational and clinical development work for LCZ-696; Entresto

Institute for Cardiovascular Disease Research

    Challenge the conventional. Create the exceptional. No Limits.